Cutaneous Reactions After SARS-CoV-2 Vaccination

A Cross-sectional Spanish Nationwide Study of 405 Cases

A. Català; C. Muñoz-Santos; C. Galván-Casas; M. Roncero Riesco; D. Revilla Nebreda; A. Solá-Truyols; P. Giavedoni; M. Llamas-Velasco; C. González-Cruz; X. Cubiró; R. Ruíz-Villaverde; S. Gómez-Armayones; M.P. Gil Mateo; D. Pesqué; O. Marcantonio; D. Fernández-Nieto; J. Romaní; N. Iglesias Pena; L. Carnero Gonzalez; J. Tercedor-Sanchez; G. Carretero; T. Masat-Ticó; P. Rodríguez-Jiménez; A.M. Gimenez-Arnau; M. Utrera-Busquets; E. Vargas Laguna; A.G. Angulo Menéndez; E. San Juan Lasser; M. Iglesias-Sancho; L. Alonso Naranjo; I. Hiltun; E. Cutillas Marco; I. Polimon Olabarrieta; S. Marinero Escobedo; X. García-Navarro; M.J. Calderón Gutiérrez; G. Baeza-Hernández; L. Bou Camps; T. Toledo-Pastrana; A. Guilabert


The British Journal of Dermatology. 2022;186(1):142-152. 

In This Article

Abstract and Introduction


Background: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized.

Objective: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination.

Methods: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification.

Results: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.

Conclusions: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.


The search for an effective vaccine has been unrelenting since 31 December 2019, when the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported in China.[1] As of 4 June 2021, COVID-NMA, an international World Health Organization-supported research initiative that live-maps and reviews SARS-CoV-2 trials, had compiled 256 vaccine trials (

Vaccine development can take more than 15 years.[2] SARS-CoV-2 vaccines have had an accelerated timeline and were approved in record time,[3] showing good safety and immunogenicity profiles in randomized controlled trials (RCTs).[4–7] Currently, the European Medicines Agency (EMA) has authorized four vaccines: BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), AZD1222 (AstraZeneca) and Ad26.COV2.S (Janssen).

SARS-CoV-2 is associated with a wide spectrum of skin manifestations.[8–11] Some may appear after immunization with vaccines expressing the SARS-CoV-2 spike (S) protein. The Spanish Agency for Medicines and Health Products (AEMPS) pharmacovigilance report found that, as of 25 April 2021, of 14 290 507 vaccine doses administered in Spain (70% BNT162b2, 24% AZD1222 and 6% mRNA-1273), 1468 nonspecified cutaneous adverse events (AEs; 0·01%) had been notified.[12] Cutaneous AEs reported in clinical and postauthorization trials include local injection site reactions and local or generalized reactions beyond the injection site. Local injection site reactions, both immediate or delayed (≥ 4 days after vaccination), were the most frequent manifestation.[4–6,13–16] Apart from anaphylactic rashes,[17] less frequent cutaneous reactions have been described in case reports and small case series: urticaria, maculopapular or morbilliform rash, pityriasis rosea-like rash, chilblain-like lesions, facial dermal filler reactions, reactivation of varicella zoster virus (VZV), lichen planus, erythema multiforme and nonspecific hypersensitivity eruptions.[4,5,7,13,15,18–27] An American registry-based study analysed 414 cases after mRNA vaccination.[28] Most reactions were reported by nondermatologists and a small number of clinical images were shown.

Since the beginning of mass vaccination in Spain, dermatologists have treated skin rashes in vaccinees. The reactions were poorly characterized and some observers considered them more frequent than previously reported and mimicking some reactions described after SARS-CoV-2 infection.[8–11]

The primary objective of our study was to characterize and classify the clinical features of cutaneous reactions after SARS-CoV-2 vaccination. Secondary objectives were to identify the timing of reactions, associations with other dermatological or allergic conditions, and possible relationships with diagnoses of SARS-CoV-2 or SARS-CoV-2-associated cutaneous reactions.